1. Technical Field
The present invention relates to a stamping device for biochips and a method for the operation thereof.
2. Description of the Related Art
In biochemistry and molecular biology, almost all biological phenomena result from biomolecular recognitions and functional interactions between biomolecules and biomolecules, such as genes and genes, proteins and proteins, proteins and ligands (a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex), ligands and receptors, antibodies and antigens, enzymes and substrates, etc. Thus, studies on interactions or recognition between biomolecues is now arising as important subjects in various fields of the biological science. For example, analyses of interactions between biomolecules may allow the early diagnosis of diseases or the identification of disease causes, may lead to analyses of signaling pathways in the body and to proteomics (analysis of protein functions or roles), and may provide decisive factors for the development of high throughput screening (HTS) systems for new drugs. In addition, these studies have very important influence on the “bioelectronics” aiming to developing electronics based on biomolecules, and the “biocomputer” field using highly specific binding molecules such as DNA/RNA.
A biochip refers to a microfluidic device in which DNAs, proteins, enzymes, ligands, and/or other chemical and biological samples are highly integrated in a microarray pattern on a solid substrate (silicon, metal, glass, etc.) that is designed to rapidly detect or analyze target biomolecules at the same time on the basis of specific interaction between the target biomolecules and the surface-immobilized or arrayed molecules, thereby attaining biological information such as gene expression and association, or protein distribution, or achieving higher throughput and speed in biochemical process, reaction rate or information processing.
A biochip may be a microarray chip such as a DNA chip for detecting diseases or genes, to which microfluidics dealing with the behavior of fluids such as blood or cells in designed microchennels may be applied. It is also called lap-on-a-chip or microTas (short for micrometer(μ)-scale total analysis system). In combination with optics, microfluidics has recently developed to optofluidics. The major application of microfluidics is analysis. It requires only small volumes of samples and reagents, allow the separation and detection of target molecules at high resolution and sensitivity and at low cost, and offers short reaction and analysis times, featuring a very small size device and a thin layer. Therefore, microfluidics offers new functions of controlling association and dissociation of molecules in time and space.
If new promising drug candidates under development will be determined as being toxic by an animal test, an immense loss is generated in the time and money took to develop the drugs. This is a big problem that must be solved in the medicinal/pharmaceutical industry or the cosmetic industry. Conventional toxicity assays employ animal or tissue samples and require a lot of time and money.
As a solution to this problem, a biochip is provided for toxicity assays. It makes possible to perform toxicity assay simply and easily in advance without the need of animal tests. The DataChip (data analysis toxicology assay chip) is representative of the biochips for high-throughput toxicity screening of drug candidates. In this regard, DataChip is prepared by spotting a collagen-encapsulated cell suspension atop each collagen spot overlaid with hyaluronan and covering the DataChip slide with the collagen-gel drops containing MCF7 cells with a sterile glass slide. When the chip is placed in an incubator, the cells grow in a three-dimensional manner. For immediate toxicity assay, various chemicals or drug candidates may be placed on the hepatic cells which are encapsulated in the collagen spots on the chip
Further, the toxicity of drug candidates was also studied with a model emulating the human liver because most drugs are metabolized in the liver. Even if a drug is non-toxic, its metabolites are generated by the liver. The MetaChip mimics the effects of metabolism in the human liver where drugs are metabolized. In the MetaChip, metabolism starts immediately after liver enzymes are exposed to drug candidates at respective spots on the chip slide. The two chips, MetaChip and DataChip may be used in combination. When combined with the MetaChip in a sandwich pattern, the DataChip can analyze the metabolites produced by the MetaChip and determine whether the metabolites are toxic or not. Thus, the fusion of these two chips allows high throughput screening (HTS) makes it possible to apply any type of cellular meolecules to the DataChip. Thus, cells of other organs as well as hepatic cells can be tested. For example, the conjunction of the DataChip with the MetaChip enables various compounds to be assayed for toxicity to dermal cells, thus finding applications in the development of cosmetics.
Nowadays, drug candidates can be, as described above, assayed for toxicity using a combination of the DataChip and the MetaChip in a sandwich pattern. The conjunction of the DataChip with the MetaChip is usually achieved by immobilizing the chips to respective stamping jigs, followed by combining the chips with each other with the position adjusted by a pin. After the combined DataChip and MetaChip is fixed, the upper frame is removed to give a biochip, a combination of the DataChip and the MetaChip. However, manual stamping processes are relatively poor in efficiency upon repetition and do not ensure accurate positioning and conjunction for the DataChip and the MetaChip, decreasing the reliability of the toxicity assay. In addition, manual stamping processes are too bothersome because they must be individually conducted for various drug candidates, as well as producing problems in accuracy and reliability.